Solution structure of selenoprotein W and NMR analysis of its interaction with 14-3-3 proteins

Finn L. Aachmann, Dmitri E. Fomenko, Alice Soragni, Vadim N. Gladyshev, Alexander Dikiy

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Abstract

Selenium is a trace element with significant biomedical potential. It is essential in mammals due to its occurrence in several proteins in the form of selenocysteine (Sec). One of the most abundant mammalian Sec-containing proteins is seleno-protein W (SelW). This protein of unknown function has a broad expression pattern and contains a candidate CXXU (where U represents Sec) redox motif. Here, we report the solution structure of the Sec13 → Cys variant of mouse SelW determined through high resolution NMR spectroscopy. The protein has a thioredoxin-like fold with the CXXU motif located in an exposed loop similarly to the redox-active site in thioredoxin. Protein dynamics studies revealed the rigidity of the protein backbone and mobility of two external loops and suggested a role of these loops in interaction with SelW partners. Molecular modeling of structures of other members of the Rdx family based on the SelW structure identified new conserved features in these proteins, including an aromatic cluster and interacting loops. Our previous study suggested an interaction between SelW and 14-3-3 proteins. In the present work, with the aid of NMR spectroscopy, we demonstrated specificity of this interaction and identified mobile loops in SelW as interacting surfaces. This finding suggests that 14-3-3 are redox-regulated proteins.

Original languageEnglish (US)
Pages (from-to)37036-37044
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number51
DOIs
StatePublished - Dec 21 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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